Design and synthesis of novel small molecule CCR2 antagonists: evaluation of 4-aminopiperidine derivatives.

A novel N-(2-oxo-2-(piperidin-4-ylamino)ethyl)-3-(trifluoromethyl)benzamide series of human CCR2 chemokine receptor antagonists was identified. With a pharmacophore model based on known CCR2 antagonists a new core scaffold was designed, analogues of it synthesized and structure­affinity relationship studies derived yielding a new high affinity CCR2 antagonist N-(2-((1-(4-(3-methoxyphenyl)cyclohexyl)piperidin-4-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide.

Darwin's species category realism.

Ever since Charles Darwin's On the Origin of Species was published, the received view has been that Darwin literally thought of species as not extra-mentally real. In 1969 Michael Ghiselin upset the received view by interpreting Darwin to mean that species taxa are indeed real but not the species category. In 1985 John Beatty took Ghiselin's thesis a step further by providing a strategy theory to explain why Darwin would say one thing (his repeated nominalistic definition of species) and do another (hold that species taxa are real). In the present paper I attempt to take this line of interpretation to a new level. Guided by the principle of charity, I provide and analyze a considerable amount of evidence from Darwin's mature writings (both private and published) to show that (contra Ghiselin and Beatty) Darwin did not simply accept the species delimitations of his fellow naturalists but actually employed, repeatedly and consistently, a species concept in a thoroughly modern sense, albeit with an implicit definition, a concept uniquely his own and fully in accord with his theory of evolution by natural selection. This implicit concept and definition is carefully reconstructed in the present paper. A new strategy theory is then provided to account for why Darwin would define species (both taxa and category) nominalistically on the one hand but delimit species realistically on the other.

In vivo evaluation of root canal sealer distribution.

The effectiveness of sealer placement and its distribution in the prepared root canal system by an energized ultrasonic file was evaluated in vivo. One hundred patients had sealer placed into prepared root canals with either the master gutta-percha cone or an ultrasonic file. Before placement of sealer with the file, canals were irrigated, debrided, and flushed with water for 10 s and an energized #20 ultrasonic file at 1.0 mm from the working length. Canals were obturated with gutta-percha using lateral condensation, and evaluations were based on the presence or absence of sealer-filled accessory canals. Chi-square analysis showed that a statistically significant difference existed in the number of radiographically visible accessory canals filled when the ultrasonic file was used to place the sealer.

Survey of endodontic retreatment methods used to remove intraradicular posts.

A survey was conducted to determine the frequency and popularity of contemporary methods used in endodontic retreatment to remove intraradicular posts. Opinions and rationales were also sought for the choice of surgical management instead of nonsurgical retreatment. A questionnaire was sent to 571 active Diplomates of the American Board of Endodontics with 324 members responding (56.7%). Hand instruments, such as hemostats or special forceps, were the most commonly used, often in conjunction with ultrasonic or sonic vibration to loosen the post or break down the cement interface. A wide range of rationales was identified for the use of surgical retreatment methods, with failure to remove the post after reasonable nonsurgical efforts being the most often cited.

Revisiting the post puller.

The removal of an intraradicular post is frequently part of retreatment and the fabrication of a new coronal restoration. This article highlights the use of a post puller for safe and effective removal of an intraradicular post in conjunction with retreatment.